The document discusses recurrence and treatment of epithelial ovarian cancer. Relapse is common, occurring in up to 60% of patients, and the platinum-free interval is a predictor of response and prognosis. For platinum-sensitive disease, combination chemotherapy like carboplatin and paclitaxel is superior to single agents and retreatment is often successful. For platinum-resistant disease, single agents or adding bevacizumab to chemotherapy can improve survival and response rates. Further lines of chemotherapy are shown to improve survival compared to best supportive care.

1. Dr. Shadi Alkhayyat. MBBS,FRCPC
Assistant Professor Of Medicine and Oncology
King Abdulaziz University

2. Overview
 Statistics.
 Defining Recurrence.
 Discussion will be limited to Epithelial Ovarian
Cancer.
 Platinum-Sensitive Ovarian Cancer.
 Platinum-Resistant Ovarian Cancer.

5.  Carboplatin and Paclitaxel standard first line.
 Follow up :
3-monthly review for 2 years.
6-monthly review for 3 years.
Annual review subsequently.
 Each visit ( clinical assessment , +/- CA 125).
 No clear evidence for routine CT radiological
assessment.

6.  Relapse is common in ovarian cancer.
 Up to 60%.
 Platinum-Free Interval:
1- Predictor for response to chemotherapy.
2- Prognostic factors for PFS and OS.
3- Predictor for outcome with cytoreduction.

7. Relapse
 CA 125 is used to follow patient with ovarian cancer.
 CA 125 rises 3-4 months before clinical symptoms.
 Serologic relapse.
 MRC OVO5/EORTC 55955
 Early versus Delayed treatment.
 1442 patients were randomized to early versus delayed
second line treatment.

8. MRC OV05/EORTC 55955
Rushtin G,Volume 376, No. 9747, p1155–1163, 2 October 2010

9. MRC OV05/EORTC 55955
Conclusion
 Early chemotherapy did not improve overall survival
 It was associated with mild worsening in quality of life.

10. Platinum-Free Interval
Platinum-Sensitive Disease Platinum-Resistant Disease
 Interval is 6 months or more  Interval is less than 6
months.
 Progression while on
chemotherapy
(Refractory ovarian cancer)

11. Platinum-Sensitive Disease
 Retreatment with same protocol.
 Combination is superior to single agent.
 Secondary cytoreduction.
 Multiple combinations
Carboplatin and Paclitaxel
Carboplatin and Liposomal doxorubicin
Carboplatin and Gemcitabine.

12. Gynecologic Cancer Intergroup
 ORR 47% Vs 31%
 PFS 8.6 m Vs 5.8 m
 OS 18m Vs 17.3m

13. Gynecologic Cancer Intergroup

14. ICON 4/AGO-OVAR 2.2

15. ICON 4/AGO-OVAR 2.2
Parmar MK, et al. Lancet. 2003;361:2099-2106

16. CALYPSO Trial
 PFS 11.3m Vs 9.4m
 OS 33m Vs 31m
 Equivalent data with
less side effects.
Waqner U, Br J Cancer 2012 Aug 7;107(4):588-91.

17. CALYPSO Trial
Waqner U, Br J Cancer 2012 Aug 7;107(4):588-91

18. Trabectedin
 If platinum can not be used, combination of
Liposomal doxorubicin and Trabectedin is an option.
 OVA-301 showed better ORR, PFS with no difference
on OS.

19. Patients who are not candidate for
combination chemotherapy
 Single agent showed good response.
 Multiple agent are approved
1- Topotecan 2- Gemcitabine.
3- Liposomal Doxorubicin
4- Trabectedin 5- Nab-Paclitaxel

20. Role of Bevacizumab
 Bevacizumab is an angiogenic inhibitor.
 Ovarian cancer expresses VEGF and VEGF receptors.
 In GOG 170D, Bevacizumab shows response as single
agent.
Eskender R, Biologics. 2011; 5: 1–5.

21. OCEAN Trial
Aghajanian C, J Clin Oncol. 2012 Jun 10;30(17):2039-45

22. OCEAN Trial
Aghajanian C, J Clin Oncol. 2012 Jun 10;30(17):2039-45

23. Platinum-Resistant Disease
 Single agent is more preferable.
 Bevacizumab has better role in combination.
 Cochrane review:
Paclitaxel
Liposomal Doxorubicin
Topotecan
 Depends on Initial therapy, side effects profile.

24.  Other single agent used are:
Gemcitabine
Etoposide
Docetaxel
Pemetrexate

25. Role of Bevacizumab
 As monotherapy, GOG 170D had limited number who
showed response.
 In ASCO 2012,
Bevacizumab showed significant improve in ORR and
PFS.

26. AURELIA Study
Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

27. AURELIA Study
Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

28. AURELIA Study
Progression-free
Survival
Overall Response Rate
10 months Vs 4 months52% Vs 29%Paclitaxel
6 months Vs 2 months23% Vs 3%Topotecan
5 months Vs 4 Months18% Vs 8%Liposomal Doxorubicin
Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

29. Combination Chemotherapy
 In GINECO trial,
Paclitaxel
Platinum Resistant
Cancer
Paclitaxel and Topotecan Paclitaxel and Carboplatin

30.  Overall response rate similar.
 Progression-Free Survival not different
 Febrile neutropenia increased 4- times in combination
arm.

31. How long to continue therapy?
 Survival improved with chemotherapy compared to
best supportive care.
Overall
Survival BSC
Overall Survival
Chemotherapy
Line of Chemotherapy
4 months14 monthsSecond Line
3 months11 monthsThird Line
3 months8 monthsFourth Line

32.  Hormonal therapy:
Fulvestrant, Tamoxifen or Letrozole.
 Targeted therapy.

33. Summary
 Relapse is common in ovarian cancer.
 Platinum-Free Interval
 Cytoreduction
 Platinum Sensitive Disease:
Combination is superior to single agent.
Retreatment is usually successful.

34.  Platinum Resistant Disease:
Single agent depending on initial chemotherapy
and side effects.
Adding Bevacizumab to single chemotherapy
improve survival and response.
 Further lines improve survival.
 Patient performance status need to be considered